There is a rapidly-growing need to identify evidence-based, safe, and effective co-treatment regimens for HIV-related tuberculosis (TB) among patients who require protease inhibitor-based antiretroviral therapy. This study will compare three alternative co-treatment options among participants in high TB endemic resource-constrained settings, in which one co-treatment option explores if an additional anti-HIV drug needs to be used when patients are being treated with a protease inhibitor together with rifabutin-based anti-TB treatment.

Accrual will take place in two accrual periods. Accrual period 1 will enroll 60 participants who will undergo an initial dose-finding period before continuing regular study follow-up. Once the review of the dose-finding pharmacokinetic and safety data from accrual period 1 participants is completed, accrual period 2 will begin.

20 to 30 mg/kg orally once daily (not to exceed 2 g per day) from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).

Other Name: PZA

Drug: Ethambutol

15 to 20 mg/kg orally once daily from entry through Week 8 study visit (or until completion of intensive TB treatment as determined after dose adjustment in accrual period 1 participants).

Other Name: EMB

Drug: Rifabutin

300 mg of rifabutin orally once until LPV/RTV is started; then the dose will be reduced to 150 mg daily from the start of LPV/RTV through Week 24.

Other Name: RBT

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection

CD4+/CD8+ T-cell count obtained within 30 days prior to study entry

Confirmed or probable pulmonary or extrapulmonary TB (more information on the criterion can be found in the protocol)

Chest x-ray within 30 days prior to study entry.

A PI-based antiretroviral (ART) regimen is required, as determined by the participant's primary clinician/clinical facility.

Certain laboratory values obtained within 14 days prior to study entry (more information on the criterion can be found in the protocol)

For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry and 72 hours of starting study medications.

Willing to use acceptable methods of contraception while on study drugs and for 6 weeks after stopping these drugs.

Karnofsky performance score > 40 within 14 days prior to study entry, and likelihood of survival, in the opinion of the site investigator, for at least 6 months.

Ability to swallow oral medications.

Ability and willingness of participant or legal guardian/representative to provide informed consent.

Exclusion Criteria:

History of completed TB treatment and resolution of TB symptoms less than 1 year prior to the current TB episode at study entry, or incomplete treatment for a prior episode of TB (i.e., defaulted past TB treatment) at any time prior to the current TB episode.

Participants infected with a rifamycin resistant strain of TB (more information on the criterion can be found in the protocol).

Receipt of more than 28 cumulative days of anti-TB treatment for the current TB episode prior to study entry.

Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Active illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry, or that in the opinion of the site investigator, might otherwise interfere with adherence to study requirements.

Pregnant or breastfeeding.

Anticipated receipt of prohibited medications (more information on the criterion can be found in the protocol).

Known intolerance/allergy/sensitivity or any hypersensitivity to components of study drugs or their formulations.

History of close contact with known MDR or XDR TB patients at any time prior to study entry.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01601626